PFAS and Phthalate/DINCH Exposure in Association with Age at Menarche in Teenagers of the HBM4EU Aligned Studies

Abstract

Early puberty has been found to be associated with adverse health outcomes such as metabolic and cardiovascular diseases and hormone-dependent cancers. The decrease in age at menarche observed during the past decades has been linked to an increased exposure to endocrine-disrupting compounds (EDCs). Evidence for the association between PFAS and phthalate exposure and menarche onset, however, is inconsistent. We studied the association between PFAS and phthalate/DINCH exposure and age at menarche using data of 514 teenagers (12 to 18 years) from four aligned studies of the Human Biomonitoring for Europe initiative (HBM4EU): Riksmaten Adolescents 2016-2017 (Sweden), PCB cohort (follow-up; Slovakia), GerES V-sub (Germany), and FLEHS IV (Belgium). PFAS concentrations were measured in blood, and phthalate/DINCH concentrations in urine. We assessed the role of each individual pollutant within the context of the others, by using different multi-pollutant approaches, adjusting for age, age- and sex-standardized body mass index z-score and household educational level. Exposure to di(2-ethylhexyl) phthalate (DEHP), especially mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), was associated with an earlier age at menarche, with estimates per interquartile fold change in 5OH-MEHP ranging from -0.34 to -0.12 years in the different models. Findings from this study indicated associations between age at menarche and some specific EDCs at concentrations detected in the general European population, but due to the study design (menarche onset preceded the chemical measurements), caution is needed in the interpretation of causality.

Keywords: DINCH; HBM4EU; PFAS; age at menarche; multi-pollutant models; phthalates.

Figure 1

Associations between PFAS concentrations (in serum/plasma) and phthalate/DINCH concentrations (in urine) and age at menarche in female teenagers (12–18 years) of the HBM4EU aligned studies, estimated by the different statistical methods. Estimates (with 95% CI) represent the change in age at menarche (years) per interquartile fold change (IQFc) in chemical concentrations, adjusted for other chemicals (except in the single-pollutant MLR), study, age, BMI z-score, and highest educational level of the household. BKMR results are the estimates obtained when fixing other chemicals at their median value. Abbreviations: MLR = multiple linear regression; ENET = elastic net; BAS = Bayesian model averaging using Bayesian adaptive sampling; BKMR = Bayesian kernel machine regression.